The recent demonstration of benzodiazepine specific receptors in brain suggests that at least some of the behavioral and physiological effects of these tranquilizer drugs are mediated through a specific receptor. These recent observations have prompted the search for endogenous ligands in brain that specifically interact with the benzodiazepine receptor, with the goal of elucidating and characterizing an anxiety mediating system. Studies thus far conducted have led to the isolation and identification of the two purine derivatives, inosine and hypoxanthine that competitively inhibit 3H diazepam binding to rat brain synaptic membranes. In vivo pharmacological studies are in progress aimed at determining whether inosine and hypoxanthine represent the physiologically relevant endogenous ligands for the benzodiazepine receptors. Recently it has been suggested that a specific protein may bind the benzodiazepine receptor and we have begun work on its isolation and characterization. Future work on this protein coupled with further characterization of inosine and hypoxanthine binding should provide considerable insight concerning anxiety mediating systems in brain.